Over the years, various fluid based processing techniques have been performed. Such processing techniques occur in both chemical and biological arts. Merely as an example, crystallization has been an important technique to the biological and chemical arts. Specifically, a high-quality crystal of a target can be analyzed by x-ray diffraction techniques to produce an accurate three-dimensional structure of the target. This three-dimensional structure information can then be utilized to predict functionality and behavior of the target.
In theory, the crystallization process is often simple to describe. For example, a target compound in pure form is dissolved in solvent. The chemical environment of the dissolved target material is then altered such that the target is less soluble and reverts to the solid phase in crystalline form. Such change in the chemical environment is typically accomplished by introducing a crystallizing agent that makes the target material less soluble, although changes in temperature and pressure can also influence solubility of the target material.
In practice however, forming a high quality crystal using conventional techniques is generally difficult, or sometimes impossible, requiring much trial and error and patience on the part of the researcher. A highly complex structure of even simple biological compounds often means that they are not amenable to forming a highly ordered crystalline structure. Therefore, a researcher must often be patient and methodical. The researcher also often experiments with a large number of conditions for crystallization, altering parameters such as reagents (e.g., type and concentration), sample concentration, solvent type, counter solvent type, temperature, and duration in order to grow a high quality crystal, if in fact a crystal can be grown at all. Additionally, conventional techniques are often difficult to use and monitor due to long processing times often associated with forming detecting, analyzing, crystal structures.
To overcome certain shortcomings with the conventional techniques, Hansen, et al., describe in PCT publication WO 02/082047, published Oct. 17, 2002 and herein incorporated by reference in its entirety for all purposes and the specific purposes disclosed therein and herein, a high-throughput system for screening conditions for crystallization of target materials, for example, proteins. The system is provided in a microfluidic device wherein an array of metering cells is formed by a multilayer elastomeric manufacturing process. Each metering cell comprises one or more of pairs of opposing chambers, each pair being in fluid communication with the other through an interconnecting microfluidic channel, one chamber containing a protein solution, and the other, opposing chamber, containing a crystallization reagent. Along the channel, a valve is situated to keep the contents of opposing chambers from each other until the valve is opened, thus allowing free interface diffusion to occur between the opposing chambers through the interconnecting microfluidic channel. As the opposing chambers approach equilibrium with respect to crystallization and protein concentrations as free interface diffusion progresses, it is hoped that the protein will, at some point, form a crystal. The microfluidic devices taught by Hansen et al. are have arrays of metering cells containing chambers for conducting protein crystallization experiments therein. Use of such arrays in turn provides for high-throughput testing of numerous conditions for protein crystallization which require analysis.
From the above, it is seen that improved techniques for processing and operating microfluidic chips are highly desired.